A discussion of the pathogenesis of type 2 diabetes mellitus must start with a review
of mechanisms involved in the maintenance of normal glucose homeostasis in the basal
or postabsorptive state (10–12 h overnight fast) and following ingestion of a typical
mixed meal [
![Figure thumbnail gr1]()
1
,
2
,
3
,
4
,
5
,
6
,
7
,
8
,
9
]. In the postabsorptive state the majority of total body glucose disposal takes place
in insulin-independent tissues. Thus, approximately 50% of all glucose use occurs
in the brain, which is insulin-independent and becomes saturated at a plasma glucose
concentration of approximately 40 mg/dL [
[10]
]. Another 25% of glucose disposal occurs in the splanchnic area (liver plus gastrointestinal
tissues), which is also insulin-independent. The remaining 25% of glucose use in the
postabsorptive state takes place in insulin-dependent tissues, primarily muscle, and
to a lesser extent adipose tissue. Basal glucose use, approximately 2.0 mg/kg/min,
is precisely matched by the rate of endogenous glucose production (Fig. 1). Approximately 85% of endogenous glucose production is derived from the liver, and
the remaining 15% is produced by the kidney. Glycogenolysis and gluconeogenesis contribute
equally to the basal rate of hepatic glucose production.
Fig. 1Postabsorptive state. Glucose production and glucose use in the normal human in the
postabsorptive state. (From DeFronzo RA. Pathogenesis of type 2 diabetes mellitus: metabolic and molecular implications
for identifying diabetes genes. Diabetes 1997;5:117–9; with permission.)
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